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Arsenopyrite and pyrite often coexist in metal deposits and tailings, thus simultaneous bioleaching of both sulfides has economic (as well as environmental) significance. Important targets in bio-oxidation operations are high solubilization rates and minimized accumulation of Fe(III)/As-bearing secondary products. This study investigated the role of pyrite bioleaching in the enhancement of arsenopyrite dissolution. At a pyrite to arsenopyrite mass ratio of 1:1, 93.6% of As and 93.0% of Fe were solubilized. The results show that pyrite bio-oxidation can promote arsenopyrite dissolution, enhance S0 bio-oxidation, and inhibit the formation of jarosites, tooeleite, and amorphous ferric arsenate. The dry weight of the pyrite & arsenopyrite residue was reduced by 95.1% after bioleaching, compared to the initial load, while only 5% weight loss was observed when pyrite was absent. A biofilm was formed on the arsenopyrite surface in the presence of pyrite, while a dense passivation layer was observed in the absence of pyrite. As(III) (as As2O3) was a dominant As species in the pyrite & arsenopyrite residue. Novel and detailed findings are presented on arsenopyrite bio-dissolution in the presence of pyrite, and the presented approach could contribute to the development of novel cost-effective extractive bioprocesses. ENVIRONMENTAL IMPLICATION: The oxidation of arsenopyrite presents significant environmental hazards, as it can contribute to acid mine drainage generation and arsenic mobilization from sulfidic mine wastes. Bioleaching is a proven cost-effective and environmentally friendly extractive technology, which has been applied for decades in metal recovery from minerals or tailings. In this work, efficient extraction of arsenic from arsenopyrite bioleaching was presented through coupling the process with bio-oxidation of pyrite, resulting in lowered accumulation of hazardous and metastable Fe(III)/As-bearing secondary phases. The results could help improve current biomining operations and/or contribute to the development of novel cost-effective bioprocesses for metal extraction.
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Arsenicales , Compuestos de Hierro , Hierro , Minerales , Sulfuros , Sulfuros/química , Hierro/química , Arsenicales/química , Cinética , Minerales/química , Compuestos de Hierro/química , Oxidación-Reducción , Solubilidad , Arsénico/química , Biopelículas , Acidithiobacillus/metabolismoRESUMEN
The first example of an electrochemical multicomponent synthesis of selenium-containing compounds with inexpensive and abundant elemental selenium as the selenating reagent was developed. A variety of selenazol-2-amines were constructed in high yields with good functional group tolerance under metal-free and chemical oxidant-free conditions.
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The sources and health risk variation of heavy metals (HMs) in sediments of Liujiang River Basin were investigated seasonally to clear the control of HMs contamination in karst rivers. The results revealed the exogenous input of HMs should be more prominent in wet season, due to the higher concentration and EF values. PMF identified HMs were mainly from natural, mining and industrial sources. The input of exogenous HMs were influenced by mining and industrial sources in wet season, but primarily by industrial sources in dry season. HI values were overall below 1, suggesting the relatively low non-carcinogenic risk. The TCR values of HMs were generally beyond 10-6, particularly those of As and Cr even exceeded 10-4 for children, which expressed a high carcinogenic risk. The sources components of As and Cr suggested preventing the migration of mining contaminants and limiting industrial emission should be essential to Liujiang River Basin.
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Metales Pesados , Contaminantes Químicos del Agua , Niño , Humanos , Ríos , Monitoreo del Ambiente/métodos , Contaminantes Químicos del Agua/análisis , Medición de Riesgo , Metales Pesados/análisis , China , Sedimentos GeológicosRESUMEN
MFSD7b belongs to the Major Facilitator Superfamily of transporters that transport small molecules. Two isoforms of MFSD7b have been identified and they are reported to be heme exporters that play a crucial role in maintaining the cytosolic and mitochondrial heme levels, respectively. Mutations of MFSD7b (also known as FLVCR1) have been linked to retinitis pigmentosa, posterior column ataxia, and hereditary sensory and autonomic neuropathy. Although MFSD7b functions have been linked to heme detoxification by exporting excess heme from erythroid cells, it is ubiquitously expressed with a high level in the kidney, gastrointestinal tract, lungs, liver, and brain. Here, we showed that MFSD7b functions as a facilitative choline transporter. Expression of MFSD7b slightly but significantly increased choline import, while its knockdown reduced choline influx in mammalian cells. The influx of choline transported by MFSD7b is dependent on the expression of choline metabolizing enzymes such as choline kinase (CHKA) and intracellular choline levels, but it is independent of gradient of cations. Additionally, we showed that choline transport function of Mfsd7b is conserved from fly to man. Employing our transport assays, we showed that missense mutations of MFSD7b caused reduced choline transport functions. Our results show that MFSD7b functions as a facilitative choline transporter in mammalian cells.
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Colina , Proteínas de Transporte de Membrana , Mutación Missense , Animales , Humanos , Colina/metabolismo , Hemo , Mamíferos , Proteínas de Transporte de Membrana/genéticaRESUMEN
Background: Glioma is a prevalent and lethal brain malignancy; despite current treatment options, the prognosis remains poor. Therefore, immunotherapy has emerged as a promising therapeutic strategy. However, research trends and hotspots in glioma immunotherapy have not been systematically analyzed. This study aimed to elucidate global research trends and knowledge structures regarding immunotherapy for glioma using bibliometric analysis. Methods: Publications related to immunotherapy for glioma from 2000-2023 were retrieved from Web of Science Core Collection database (WoSCC). We conducted quantitative analysis and visualization of research trends using various tools, including VOSviewer (1.6.18), CiteSpace (5.7 R3), Microsoft Charticulator, and the Bibliometrix package in R. Results: A total of 4910 publications were included. The number of annual publications exhibited an obvious upward trend since 2019. The USA was the dominant country in terms of publication output and centrality. Frontiers in Immunology published the most articles. Harvard Medical School ranked first in productivity among institutions. Sampson, John H. Ph.D. is the most prolific author in the field with 88 articles and a total of 7055 citations. Clinical Cancer Research has the largest total number and impact factor. Analysis of keywords showed immunotherapy, glioblastoma, immunotherapy, and clinical trials as hot topics. The tumor microenvironment, cell death pathways, chimeric antigen receptor engineering, tumor-associated macrophages, and nivolumab treatment represent indicating shifts in the direction of future glioma immunotherapy development. Conclusion: This bibliometric analysis systematically delineated global landscapes and emerging trends in glioma immunotherapy research. This study highlighted the prominence of Chimeric Antigen Receptor T-cell (CAR-T), Programmed Death-1 (PD-1), and nivolumab in current glioma immunotherapy research. The growing emphasis on specific neoantigens and prognostic tumor markers suggests potential avenues for future exploration. Furthermore, the data underscores the importance of strengthened international collaboration in advancing the field.
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Glioma , Receptores Quiméricos de Antígenos , Humanos , Nivolumab , Glioma/terapia , Inmunoterapia , Bibliometría , Microambiente TumoralRESUMEN
OBJECTIVE: The purpose of this study was to investigate the role of the unfolded protein response, specifically the inositol-requiring enzyme 1 (IRE1) signaling pathway, in hypoxia-induced autophagy in human umbilical venous endothelial cells (HUVECs). METHODS: The expression of IRE1 and autophagy relative protein in HUVECs with hypoxia was explored by Western blotting, qRT-PCR and confocal microscopy. Further, we evaluated the biological effects of HUVECs by tube formation assay and wound healing assay in vitro. Finally, we examined the function of IRE1 in local blood vessels through animal models. RESULTS: Hypoxia activated the IRE1 signaling pathway and induced autophagy in a time-dependent manner in HUVECs and further influenced the biological effects of HUVECs. Intraperitoneal injection of IRE1 inhibitors inhibited local vascular autophagy levels and lipid accumulation in model animals. CONCLUSION: Hypoxia can induce autophagy and activate the IRE1 signaling pathway in HUVECs and the IRE1 signaling pathway is involved in autophagy in hypoxic conditions.
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Proteínas Serina-Treonina Quinasas , Respuesta de Proteína Desplegada , Animales , Humanos , Autofagia , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Hipoxia , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismoRESUMEN
Artificial knee arthroplasty, as the most effective method for the treatment of end-stage joint diseases such as knee osteoarthritis and rheumatoid arthritis, is widely used in the field of joint surgery. At present, Finite element analysis (FEA) has been widely used in artificial knee replacement biomechanical research. This review presents the current hotspots for the application of FEA in the field of artificial knee replacement by reviewing the existing research literature and, by comparison, summarizes guidance and recommendations for artificial knee replacement surgery. We believe that lower contact stress can produce less wear and complications when components move against each other, in the process of total knee arthroplasty (TKA), mobile-bearing prostheses reduce the contact surface stress of the tibial-femoral joint compared with fixed-bearing prostheses, thus reducing the wear of the polyethylene insert. Compared with mechanical alignment, kinematic alignment reduces the maximum stress and maximum strain of the femoral component and polyethylene insert in TKA, and the lower stress reduces the wear of the joint contact surface and prolongs the life of the prosthesis. In the unicompartmental knee arthroplasty (UKA), the femoral and tibial components of mobile-bearing prostheses have better conformity, which can reduce the wear of the components, while local stress concentration caused by excessive overconformity of fixed-bearing prostheses should be avoided in UKA to prevent accelerated wear of the components, the mobile-bearing prosthesis maintained in the coronal position from 4° varus to 4° valgus and the fixed-bearing prosthesis implanted in the neutral position (0°) are recommended. In revision total knee arthroplasty (RTKA), the stem implant design should maintain the best balance between preserving bone and reducing stress around the prosthesis after implantation. Compared with cemented stems, cementless press-fit femoral stems show higher fretting, for tibial plateau bone defects, porous metal blocks are more effective in stress dispersion. Finally, compared with traditional mechanical research methods, FEA methods can yield relatively accurate simulations, which could compensate for the deficiencies of traditional mechanics in knee joint research. Thus, FEA has great potential for applications in the field of medicine.
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Objective.Ultrasound has been shown to modulate the activity of retinal ganglion cells (RGCs) in mice, but the mechanism remains poorly understood. This study aims to address this question.Approach.Multi-electrode recordings together with pharmacological methods were used to investigate the possible cellular/circuitry mechanism(s) underlying the neuronal modulation induced by low-frequency (1 MHz), low-intensity (ISPTA0.5 W cm-2) ultrasound stimulation.Main results.We found that ultrasound activated mechanosensitive channels (transient receptor potential vanilloid 4 (TRPV4) channels are involved) in Müller cells, causing the release of glutamate, which acts on the extrasynapticN-methyl-D-aspartate receptors of RGCs, thus leading to the modulation of neuronal activity.Significance.Our results reveal a novel mechanism of low-frequency, low-intensity ultrasound modulation, involving TRPV4 as a mechanosensitive target for ultrasound and glutamate as an essential mediator of neuron-glia communication. These findings also demonstrate that the mechanical-force-mediated pathway is important for retinal signal modulation during visual processes, such as visual accommodation.
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Retina , Canales Catiónicos TRPV , Ratones , Animales , Canales Catiónicos TRPV/metabolismo , Retina/metabolismo , Células Ganglionares de la Retina/fisiología , Neuroglía/metabolismo , Glutamatos/metabolismoRESUMEN
Previous data have linked omega-3 fatty acids with risk of dementia. We aimed to assess the longitudinal relationships of omega-3 polyunsaturated fatty acid intake as well as blood biomarkers with risk of Alzheimer's disease (AD), dementia, or cognitive decline. Longitudinal data were derived from 1135 participants without dementia (mean age = 73 y) in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort to evaluate the associations of omega-3 fatty acid supplementation and blood biomarkers with incident AD during the 6-y follow-up. A meta-analysis of published cohort studies was further conducted to test the longitudinal relationships of dietary intake of omega-3 and its peripheral markers with all-cause dementia or cognitive decline. Causal dose-response analyses were conducted using the robust error meta-regression model. In the ADNI cohort, long-term users of omega-3 fatty acid supplements exhibited a 64% reduced risk of AD (hazard ratio: 0.36, 95% confidence interval: 0.18, 0.72; P = 0.004). After incorporating 48 longitudinal studies involving 103,651 participants, a moderate-to-high level of evidence suggested that dietary intake of omega-3 fatty acids could lower risk of all-cause dementia or cognitive decline by â¼20%, especially for docosahexaenoic acid (DHA) intake (relative risk [RR]: 0.82, I2 = 63.6%, P = 0.001) and for studies that were adjusted for apolipoprotein APOE ε4 status (RR: 0.83, I2 = 65%, P = 0.006). Each increment of 0.1 g/d of DHA or eicosapentaenoic acid (EPA) intake was associated with an 8% â¼ 9.9% (Plinear < 0.0005) lower risk of cognitive decline. Moderate-to-high levels of evidence indicated that elevated levels of plasma EPA (RR: 0.88, I2 = 38.1%) and erythrocyte membrane DHA (RR: 0.94, I2 = 0.4%) were associated with a lower risk of cognitive decline. Dietary intake or long-term supplementation of omega-3 fatty acids may help reduce risk of AD or cognitive decline.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Ácidos Grasos Omega-3 , Humanos , Anciano , Enfermedad de Alzheimer/prevención & control , Estudios Prospectivos , Ácidos Docosahexaenoicos , Ácido Eicosapentaenoico , Disfunción Cognitiva/prevención & control , Suplementos Dietéticos , Estudios de Cohortes , Ingestión de AlimentosRESUMEN
The first example of paired electrolysis-enabled cyanation of diaryl diselenides, with KSCN as the green cyanating agent, has been developed. A broad range of aryl selenocyanates can be efficiently synthesized under chemical-oxidant- and additive-free, energy-saving and mild conditions.
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Dengue virus (DENV) is a flavivirus causing an estimated 390 million infections per year around the world. Despite the immense global health and economic impact of this virus, its true receptor(s) for internalization into live cells has not yet been identified, and no successful antivirals or treatments have been isolated to this date. This study aims to improve our understanding of virus entry routes by exploring the sialic acid-based cell surface molecule GM1a and its role in DENV infection. We studied the interaction of the virus with GM1a using fluorescence correlation spectroscopy, fluorescence crosscorrelation spectroscopy, imaging fluorescence correlation spectroscopy, amide hydrogen/deuterium exchange mass spectrometry, and isothermal titration calorimetry. Additionally, we explored the effect of this interaction on infectivity and movement of the virus during infection was explored using plaque assay and fluorescence-based imaging and single particle tracking. GM1a was deemed to interact with DENV at domain I (DI) and domain II (DII) of the E protein of the protein coat at quaternary contacts of a fully assembled virus, leading to a 10-fold and 7-fold increase in infectivity for DENV1 and DENV2 in mammalian cell systems, respectively. We determined that the interaction of the virus with GM1a triggers a speeding up of virus movement on live cell surfaces, possibly resulting from a reduction in rigidity of cellular rafts during infection. Collectively, our results suggest that GM1a functions as a coreceptor/attachment factor for DENV during infection in mammalian systems.
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Virus del Dengue , Dengue , Flavivirus , Animales , Humanos , Virus del Dengue/metabolismo , Proteínas del Envoltorio Viral/metabolismo , Gangliósidos/metabolismo , Flavivirus/metabolismo , Mamíferos/metabolismoRESUMEN
Sanghuangporus sp., a medicinal and edible homologous macrofungus known as 'forest gold', which has good effects on antitumor, hypolipidemia and the treatment of gynecological diseases. However, the natural resources of fruiting body are on the verge of depletion due to its long growth cycle and over exploitation. The growth and metabolism of macrofungi are known to depend on the diverse bacterial community. Here, we characterized the diversity and potential function of bacteria inhabiting in the fruiting body of the most widely applied S. vaninii using a combination method of high-throughput sequencing with pure culturing for the first time, and tested the biological activities of bacterial isolates, of which Illumina NovaSeq provided a more comprehensive results on the bacterial community structure. Total 33 phyla, 82 classes, 195 orders, 355 families, 601 genera and 679 species were identified in the fruiting body, and our results revealed that the community was predominated by the common Proteobacteria, Gammaproteobacteria, Burkholderiales, Methylophilaceae (partly consistent with pure-culturing findings), and was dominated by the genera of distinctive Methylotenera and Methylomonas (yet-uncultured taxa). Simultaneously, the functional analysis showed that companion bacteria were involved in the pathways of carbohydrate transport and metabolism, metabolism of terpenoids and polyketides, cell wall/membrane/envelope biogenesis, etc. Hence, it was inferred that bacteria associated with fruiting body may have the potential to adjust the growth, development and active metabolite production of host S. vaninii combined with the tested results of indole-3-acetic acid and total antioxidant capacity. Altogether, this report first provided new findings which can be inspiring for further in-depth studies to exploit bioactive microbial resources for increased production of Sanghuangporus, as well as to explore the relationship between medicinal macrofungi and their associated endophytes.
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Ascomicetos , Basidiomycota , Ascomicetos/metabolismo , Bacterias , Cuerpos Fructíferos de los Hongos/metabolismo , HumanosRESUMEN
Conservation agriculture (CA) can be an important strategy for improving soil organic carbon (SOC) and total nitrogen (TN). Numerous studies have examined SOC and TN dynamics in different cropping systems. However, there is some uncertainty regarding the relative impacts of some CA practices, and it is not always clear how other agricultural management, particularly nitrogen addition, interacts with these practices to influence SOC and TN sequestration. Thus, we conducted a global meta-analysis of 752 comparisons from 97 papers to analyze the impacts of nitrogen fertilizers and CA practices (namely crop diversification, minimal soil disturbance (no-tillage) and permanent soil cover), on SOC and TN content worldwide. Overall, our study showed the most significant increase of SOC [21.39 % (CI = 15.16 to 28.64)] and TN [54.34 % (CI = 26.19 to 96.69)] stock with CA practices compared to conventional practices in the 0-15 cm soil depth. It also showed a significant increase in SOC and TN stock with all the individual components of CA compared to conventional practices in the 0-15 cm soil depth. However, the impact of CA on SOC and TN is reduced in 0-60 cm depths compared to surface soil depths due to the limited input of crop residue deeper in the soil profile. Manure and manure mixed with mineral-N led to greater SOC sequestration [20.67 % (CI = 15.23 to 27.10) and 41.67 % (CI = 31.03 to 52.79), respectively] than mineral-N alone [9.08 % (CI = 6.44 to 11.83)]. Cropping systems that included legume residue decreased the C/N ratio. This highlights that adequate mineral-N fertilizer addition may also be required in conjunction with residue retention practices to improve SOC and TN content. Overall, these results show that CA systems that include legume residue and manure mixed with mineral-N have great potential to increase SOC and TN, particularly at 0-15 cm and 0-30 cm soil depth.
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Nitrógeno , Suelo , Agricultura/métodos , Carbono/química , Secuestro de Carbono , Fertilizantes , Estiércol , Minerales , Nitrógeno/análisis , Suelo/químicaRESUMEN
Objective. Ultrasound modulates the firing activity of retinal ganglion cells (RGCs), but the effects of lower-frequency, lower-intensity ultrasound on RGCs and underlying mechanism(s) remain poorly understood. This study aims to address these questions.Approach. Multi-electrode recordings were used in this study to record the firing sequences of RGCs in isolated mouse retinas. RGCs' background firing activities as well as their light responses were recorded with or without ultrasound stimulation. Cross-correlation analyses were performed to investigate the possible cellular/circuitry mechanism(s) underlying ultrasound modulation.Main results. It was found that ultrasound stimulation of isolated mouse retina enhanced the background activity of ON-RGCs and OFF-RGCs. In addition, background ultrasound stimulation shortened the light response latency of both ON-RGCs and OFF-RGCs, while enhancing part of the RGCs' (both ON- and OFF-subtypes) light response and decreasing that of the others. In some ON-OFF RGCs, the ON- and OFF-responses of an individual cell were oppositely modulated by the ultrasound stimulation, which suggests that ultrasound stimulation does not necessarily exert its effect directly on RGCs, but rather via its influence on other type(s) of cells. By analyzing the cross-correlation between the firing sequences of RGC pairs, it was found that concerted activity occurred during ultrasound stimulation differed from that occurred during light stimulation, in both spatial and temporal aspects. These results suggest that the cellular circuits involved in ultrasound- and light-induced concerted activities are different and glial cells may be involved in the circuit in response to ultrasound.Significance. These findings demonstrate that ultrasound affects neuronal background activity and light responsiveness, which are critical for visual information processing. These results may also imply a hitherto unrecognized role of glial cell activation in the bidirectional modulation effects of RGCs and may be critical for the nervous system.
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Luz , Células Ganglionares de la Retina , Animales , Ratones , Estimulación Luminosa , Células Ganglionares de la Retina/fisiologíaRESUMEN
CONTEXT: Mulisan decoction (MLS) is a classic formula of traditional Chinese medicine for treating hyperhidrosis. The mechanism remains unclear. OBJECTIVE: To investigate the antiperspirant effect and underlying mechanisms of MLS. MATERIALS AND METHODS: Fifty rats were divided into control, model, and three doses of MLS intervention groups (n = 10). Rats except for control group were induced diseases features of the applicable scope of MLS via i.p. reserpine (0.5 mg/kg/d) for 10 days. From day 11, MLS groups were administrated orally MLS at 0.6, 3, and 15 g/kg once a day for 14 days, respectively. After the last administration, sweating was induced in all rats via s.c. pilocarpine (25 mg/kg), the right hind foot of rats was stained, and sweat point numbers were observed. Rat serum was collected to detect IL-2, IL-6, IFN-γ, and TNF-α. Rat plasma was collected for endogenous metabolite analysis via UPLC-QE-Focus-MS. RESULTS: Rats treated with MLS presented a significant decrease in sweat point numbers (13.5%), increase in body weight (13.2%), and promotion in the balance of Th1/Th2 cytokine ratio via increasing IL-2 (38.3%), IFN-γ (20.1%), and TNF-α (22.0%) and decreasing IL-6 (24.7%) compared with the model group (p < 0.05). Plasma metabolomics disclosed 15 potential biomarkers related to model rats, of which two could be significantly reversed by MLS (p < 0.05). The involved pathways were pantothenate and CoA biosynthesis, and porphyrin metabolism. CONCLUSIONS: MLS demonstrated a good antiperspirant effect and metabolism improvement. These findings inspire more clinical study validation on immune improvement and antiperspirant effect.
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Antitranspirantes , Hiperhidrosis , Medicina Tradicional China , Animales , Antitranspirantes/farmacología , Hiperhidrosis/tratamiento farmacológico , Interleucina-2 , Interleucina-6 , Metabolómica , Ratas , Factor de Necrosis Tumoral alfaRESUMEN
The aminobenzamide is selective to class I histone deacetylases (HDACs) and displays unique tight-binding/slow-off HDAC-binding mechanism. Herein, we report a series of 9-substituted purine aminobenzamides that selectively inhibit class I HDACs. The activities in vitro showed compound 9d exhibited 12 folds more potent than MS-275 against HDAC1 isoform and showed excellent inhibitory activity on cancer cells, including HCT-116, MDA-MB-231, K562 cell lines. The metabolic stability of 9d was much better than that of the well-known HDAC inhibitor SAHA. Pulse exposure test of western blot assay demonstrated that 9a, 9d induced histone acetylation in a similar manner to MS-275. Further biological validation demonstrated that 9d prevented cell transition from G1 phase to S phase by reducing Cyclin D1, CDK2 and lifting p21, induced early apoptosis by upregulating BAX and downregulating Bcl-2 in HCT-116 cells.
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Antineoplásicos/farmacología , Benzamidas/farmacología , Inhibidores de Histona Desacetilasas/farmacología , Histona Desacetilasas/metabolismo , Purinas/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Benzamidas/síntesis química , Benzamidas/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Inhibidores de Histona Desacetilasas/síntesis química , Inhibidores de Histona Desacetilasas/química , Humanos , Simulación del Acoplamiento Molecular , Estructura Molecular , Purinas/química , Relación Estructura-ActividadRESUMEN
BACKGROUND AND PURPOSE: The present study aimed to explore whether and how omega-3 (ω-3) supplementation could interact with genetic factors to modulate cognitive functions, amyloid pathologies, and Alzheimer's disease (AD) risk. METHODS: A total of 1,670 non-demented participants (mean age 73 years, 47% females, 41% APOE ε4 carriers) were followed up for 10 years. Hierarchical regressions, linear mixed-effects models, and Cox proportional hazards models were used to examine the interaction effects of ω-3 supplementation with APOE ε4 and polygenic hazard scores, after adjusting for age, gender, education, cognitive diagnosis, insomnia, depression, anxiety, and cardiovascular risk score. RESULTS: Individuals who progress to AD during the follow-up tend to take a shorter duration of ω-3 at baseline than those stable, for whom the difference remained significant only amongst APOE ε4 carriers (p < 0.01). The interaction term (APOE ε4 × ω-3) accounted for a significant amount of variance in cognition and cerebral amyloid burden. Long-term ω-3 use protected cognition (especially memory function) and lowered amyloid burden and AD risk only amongst APOE ε4 carriers. Mediation analysis suggested that amyloid pathologies, brain reserve capacities, and brain metabolism mediated the relationships of ω-3 use with memory and global cognition for APOE ε4 (+) carriers. Similar interaction and mediation effects were also indicated amongst high-risk subjects defined by polygenic hazard scores. CONCLUSIONS: Long-term ω-3 intake may have a role in AD prevention in genetically at-risk populations.
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Enfermedad de Alzheimer , Apolipoproteína E4 , Anciano , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/prevención & control , Apolipoproteína E4/genética , Cognición , Suplementos Dietéticos , Femenino , Genotipo , Humanos , Masculino , Factores de RiesgoRESUMEN
Objective: To investigate the clinicopathological features and treatment strategies of pituicytoma. Methods: Twenty-one cases of pituicytoma were collected at the First Affiliated Hospital of Nanjing Medical University and Jinling Hospital, Nanjing, China from 2009 to 2020. The clinical data of 21 pituicytoma patients was retrospectively analyzed, and the relevant literature was reviewed. Results: Twenty-one patients aged 4 to 68 years, including 8 males and 13 females. All patients underwent surgical treatment. Histologically, the tumor was consisted almost entirely of elongate, bipolar spindle cells arranged in a fascicular or storiform pattern. Mitotic figures were rare. Immunohistochemically, tumor cells were diffusely positive for S-100 protein (21/21), vimentin (15/15) and TTF1 (14/14), while they were weakly or focally positive for GFAP (13/16) and EMA (6/12). CKpan was negative in all cases and Ki-67 proliferation index was low (<5%). Among the 18 patients with follow-up, all survived and 2 relapsed after surgery. Conclusions: Pituicytoma is a rare low-grade glioma of the sellar area. It is easily confused with other sellar tumors. Preoperative diagnosis is difficult. It needs to be confirmed by histopathology and immunohistochemistry. Microsurgery is the main treatment method at present.
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Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Craneofaringioma , Glioma/patología , Inmunohistoquímica , Neoplasias Hipofisarias/patología , Estudios RetrospectivosRESUMEN
Panax notoginseng mixture (PNM) has the characteristics of multicomponent, multitarget, and multieffect, which can cope with the multidirectional and multidimensional complex pathological process caused by hepatic ischemia/reperfusion injury (HIRI). Our animal experiments showed that PNM composed of notoginseng, dogwood, and white peony root could significantly reduce the level of aspartate transaminase and alanine aminotransferase in the blood of mice with HIRI, indicating that this preparation had a protective effect on HIRI in mice. Therefore, on this basis, the molecular mechanism of PNM intervention in HIRI was further explored by network pharmacology. First, target genes corresponding to active components and HIRI were obtained through databases such as TCMSP, Pharm Mapper, Swiss Target Prediction, GeneCards, and so on. All target genes were standardized by Uniprot database, and a total of 291 target genes with their intersection were obtained. Then, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and biological processes (BPs) of 291 target genes were obtained through the online public platform of DAVID. A total of 177 KEGG pathways and 337 BPs were obtained by setting p < 0.01 and false discovery rate <0.05. The network mapping map of components and disease targets was drawn by Cytoscape, and the top 10 Hub target genes related to HIRI were obtained. At the same time, the String database was used to obtain the protein-protein interaction dataset, which was imported into Cytoscape, and the first 10 Hub target genes were obtained. The Hub target genes obtained by the above two methods were molecular docking with their corresponding small molecule compounds through DockThor online tool. The results showed that the docking of paeoniflorin with glyceraldehyde 3-phosphate dehydrogenase (GAPDH), paeoniflorin and loganin with SRC, ginsenoside Rb1 with NR3C2, ursolic acid and oleanolic acid with IL-6, paeoniflorin docking VEGFA, and MMP9. Finally, NR3C2, SRC, and GAPDH were identified as target genes in this study by referring to relevant literature reports. After verification by immunohistochemical experiments, compared with the sham group, the above three target genes were highly expressed in the HIRI group (p < 0.01). Compared with the HIRI group, the expression of three target genes in the PNM + HIRI group was significantly decreased (p < 0.01). The results showed that PNM could protect mouse HIRI by decreasing the expression of NR3C2, SRC, and GAPDH.
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The 12-year-old patient was admitted to the hospital on September 19, 2019 for "vaginal bleeding for 2 + months and pelvic mass to be diagnosed". The patient and her family explicitly denied any previous history of diethylstilbestrol exposure. After admission, relevant examinations were conducted and hysteroscopic exploration was performed under general anesthesia. During the procedure, cervical neoplasms were extracted and pathology results indicated cervical cancer. Then, extensive transabdominal hysterectomy+bilateral salpingectomy+bilateral ovarian transposition+pelvic lymph node dissection+para-aortic lymph node sampling were performed. Postoperative pathology analysis of the removed tissue showed that clear cell carcinoma of cervix (CCAC) had infiltrated into 1/3 of the cervical stroma and there was downward involvement of the vaginal wall; the cancer metastasized to the left obturator lymph node and the left internal and external iliac lymph nodes. Immunohistochemical staining of the removed tissue showed the following results: cytokeratin 7 (+), cytokeratin 20 (-), Napsin-A (+), cell adhesion molecule CD15 (+), heatocyte nuclear factor-1 ß (+), Sal-like protein 4 (-), tumor suppressor gene P16 protein (+), estrogen receptor (+), progesterone receptor (-), tumor suppressor gene P53 protein (focal positive), tumor suppressor gene WT-1 protein (-) and Ki67 antigen (about 40% positive). The patient was diagnosed with CCAC stage â ¢C1p. Four cycles of postoperative systemic chemotherapy (fluorouracil+cisplatin) and 25 times of three-dimensional afterloading radiotherapy were performed. The patient did follow-up visits and did not show obvious signs of recurrence. The clinical manifestations of this disease are basically the same as those of cervical squamous cell carcinoma, and if the patient is younger, it can be easily misdiagnosed as dysfunctional uterine bleeding, indicating the need for differential diagnosis.